Dose-response analysis of acute hypotensive and renal effects of atrial natriuretic peptide in the rat.

Abstract

Acute treatments with synthetic atrial natriuretic peptides induce hypotension, in which several mechanisms, including renal effects, are involved. The implication of the renal vasculature and the excretory capacities in the hypotensive action of atrial natriuretic peptides are not ascertained as yet. To address this issue, the rapid time sequence of the acute effects of atrial natriuretic peptides upon renal blood flow, mean arterial pressure, heart rate, and salt and water excretion, as well as a dose-response analysis, were investigated in 38 anesthetized euvolemic rats. Doses varying from 0.25 to 2.50 micrograms of atrial natriuretic peptide were injected i.v. in 30 sec. Each dose induced a brisk and transient increase in renal blood flow, which was maximal (13%) above 1 microgram of atrial natriuretic peptide. A small reduction in mean arterial pressure, timely related to renal vasodilation, occurred at first. It was followed by a second reduction in mean arterial pressure, which was concomitant to the maximal increases in diuresis and natriuresis. It persisted over a longer period of time. The maximal hypotensive effect (-15 mmHg) was observed above 1.5 micrograms of atrial natriuretic peptide. All effects were dose-dependent. There were no changes in heart rate. In conclusion, atrial natriuretic peptides transiently induced dose-dependent increases in renal blood flow and salt and water excretion, while the mean arterial pressure decreased stepwisely. The biphasic hypotensive effect was time-related to the renal vasodilator and diuretic effects, respectively.